During embryonic days E12-14 undifferentiated metanephric mesenchyme contains cells expressing renin. The renin expression occurs before the vascularization of the kidney. Later, E17-20, large intrarenal arteries express renin, but as development continues, renin expression becomes restricted to the juxtaglomerular (JG) location found in adults. In the adult, stimuli known to increase renin synthesis result in a recruitment of the cells along the preglomerular vasculature and interstitium suggesting a plasticity to develop renin expression. This ability may be due to the developmental history of the cell. While the origin of the JG cells during embryogenesis is not known, the hypotheses are that 1) they originate from kidney cells not the invading vasculature, 2) the lineage is of smooth muscle or interstitial cells, 3) expression of renin is responsible for the JG cell development, 4) the JG cells are involved in nephrogenesis and microvascular development in the kidney. To address these hypotheses the following aims will be pursued: I) define the phenotype of the JG cells during maturation; ii) determine the origin of the JG cells; iii) identify and follow the fate of the precursors in vivo and in vitro; iv) determine whether the JG cell is necessary for normal nephrogenesis and vascular development. It is anticipated that this information will generate fundamental knowledge of kidney development and should provide new avenues for models of hypertension and kidney disease.